Assessment of the Effect of Empagliflozin (BI 10773) as Single Dose on the QT Interval in Healthy Female and Male Subjects

Assessment of the Effect of 25 mg and 200 mg of BI 10773 as Single Dose on the QT Interval in Healthy Female and Male Subjects. A Randomised, Placebo Controlled, Double-blind, Five-period Crossover Phase-I-study With Moxifloxacin as Positive Control

The objective of this study is to demonstrate that BI 10773 does not prolong the QT(c) interval more than placebo

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BI 10773 (low); Drug: BI 10773 (high); Drug: BI 10773 Placebo; Drug: Moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany
    • 1245.16.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

healthy female and male subjects

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 10773; single oral (high and low) dose per subject	Drug: BI 10773 (low); single oral dose; Drug: BI 10773 (high); single oral dose
Placebo Comparator: Placebo; 2 single oral doses per subject	Drug: BI 10773 Placebo; 2 times single dose
Active Comparator: Moxifloxacin; single oral dose per subject	Drug: Moxifloxacin; single oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Empa 25mg: Mean QTcN Change From Baseline Between 1 and 4 Hours After Dosing	Mean QTcN (heart rate-corrected QT interval, using a study population-based approach) from the ECGs obtained between 1h to 4h following drug administration minus the mean QTcN from the baseline electrocardiogram (ECGs) obtained pre-dose at each visit, for empa 25mg. Note, the treatment means presented are actually adjusted means.	60 minutes (min), 50min and 40 min before the first dose and 1 hour (h), 1.5h, 2h, 2.5h, 3h and 4h after the first dose
Empa 200mg: Mean QTcN Change From Baseline Between 1 and 4 Hours After Dosing	Mean QTcN (heart rate-corrected QT interval, using a study population-based approach) from the ECGs obtained between 1h to 4h following drug administration minus the mean QTcN from the baseline ECGs obtained pre-dose at each visit, for empa 200mg. Note, the treatment means presented are actually adjusted means.	60 minutes (min), 50min and 40 min before the first dose and 1 hour (h), 1.5h, 2h, 2.5h, 3h and 4h after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Empa 25 mg: Mean QTcN Change From Baseline Between 30 Minutes and 24 Hours After Dosing	Mean changes from baseline in QTcN from all ECGs taken between 30 minutes and 24 hours after dosings, for empa 25 mg. Note, presented means are actually adjusted means.	60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose
Empa 200 mg: Mean QTcN Change From Baseline Between 30 Minutes and 24 Hours After Dosing	Mean changes from baseline in QTcN from all ECGs taken between 30 minutes and 24 hours after dosings, for empa 200 mg. Note, presented means are actually adjusted means.	60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose
Mean QTcN Change From Baseline Between 2 and 4 Hours After Dosing	Mean changes from baseline in QTcN from all ECGs taken between 2 hours and 4 hours after dosings Note, the means presented are actually adjusted means.	60 minutes (min), 50min and 40 min before the first dose and 2 hour (h), 2.5h, 3h and 4h after the first dose
Empa 25mg: Change From Mean Baseline in QTcN at Each Time Point Between 30 Minutes and 24 Hours After Dosings	Change from mean baseline in QTcN at each time point between 30 minutes and 24 hours after dosings for empa 25mg. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum upper confidence limit value over time. For this outcome results are presented for the 24 hour timepoint as this was when the maximum value was seen. Note, the presented means are actually adjusted means.	60 minutes (min), 50min and 40 min before the first dose and 0.5 hour (h), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose
Empa 200mg: Change From Mean Baseline in QTcN at Each Time Point Between 30 Minutes and 24 Hours After Dosings	Change from mean baseline in QTcN at each time point between 30 minutes and 24 hours after dosings for empa 200mg. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum upper confidence limit value over time. For this outcome results are presented for the 2.5 hour timepoint as this was when the maximum value was seen. Note, the presented means are actually adjusted means.	60 minutes (min), 50min and 40 min before the first dose and 0.5 hour (h), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-matched Change From Placebo in QTcN Between 30 Minutes and 24 Hours After Dosing.	The time-matched change from placebo is defined per time point as the difference of the ECG measurement following administration of empa or moxifloxacin minus the average of the measurements obtained following the two administrations of placebo. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum mean value of all measurements. Results are presented for the greatest change, for empa 25mg the greatest change was seen at the 24 hour time point, for empa 200 mg and moxifloxacin the greatest change was seen at the 2.5 hour time point.	60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose
Placebo Corrected Change From Mean Baseline at Any Time Point Between 30 Minutes and 24 Hours After Dosings.	The placebo corrected change from mean baseline is defined per time point as the difference of the change from baseline for empa or moxifloxacin minus the average change from baseline obtained for the two administrations of placebo. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum mean value of all measurements. Results are presented for the greatest change, for empa 25mg the greatest change was seen at the 24 hour time point, for empa 200 mg and moxifloxacin the greatest change was seen at the 2.5 hour time point.	60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator	Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry, haematology, urinanalysis and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as adverse events (AEs). Time frame for AE reporting includes the period of first drug administration until end of study. A more detailed definition of the used time frame and MedDRA Version can be found in the AE section.	Drug administration until beginning of next sequence/end of trial, up to 48 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Ring A, Brand T, Macha S, Breithaupt-Groegler K, Simons G, Walter B, Woerle HJ, Broedl UC. The sodium glucose cotransporter 2 inhibitor empagliflozin does not prolong QT interval in a thorough QT (TQT) study. Cardiovasc Diabetol. 2013 Apr 24;12:70. doi: 10.1186/1475-2840-12-70.

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: September 3, 2010
• First Submitted That Met QC Criteria: September 3, 2010
• First Posted (Estimate): September 6, 2010

Study Record Updates

• Last Update Posted (Estimate): July 28, 2014
• Last Update Submitted That Met QC Criteria: July 25, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Sodium-Glucose Transporter 2 Inhibitors; Moxifloxacin; Empagliflozin
• Other Study ID Numbers: 1245.16; 2010-018609-13 (EudraCT Number: EudraCT)